scholarly journals Treatment with Subcritical Water-Hydrolyzed Citrus Pectin Ameliorated Cyclophosphamide-Induced Immunosuppression and Modulated Gut Microbiota Composition in ICR Mice

Molecules ◽  
2020 ◽  
Vol 25 (6) ◽  
pp. 1302 ◽  
Author(s):  
Jianbing Chen ◽  
Chengcheng Zhang ◽  
Qile Xia ◽  
Daqun Liu ◽  
Xinghe Tan ◽  
...  

Subcritical water can effectively hydrolyze pectin into smaller molecules while still maintaining its functional regions. Pectic heteropolysaccharide can mediate immune regulation; however, the possible effects of subcritical water-hydrolyzed citrus pectin (SCP) on the immune response remain unclear. Therefore, the effects of SCP on immunomodulatory functions and intestinal microbial dysbiosis were investigated using a cyclophosphamide-induced immunosuppressed mouse model. In this research, immunosuppressed ICR mice were administrated with SCP at dosages of 300/600/1200 mg/kg.bw by oral gavage, and body weight, immune organ indexes, cytokines, and gut microbiota were determined. The results showed that subcritical water treatment decreased the molecular mass and increased the content of galacturonic acid in citrus pectin hydrolysates. Meanwhile, the treatment with SCP improved immunoregulatory functional properties and bioactivities over the original citrus pectin. For example, SCP protected immune organs (accelerated recovery of immune organ indexes) and significantly enhanced the expression of immune-related cytokines (IL-2, IL-6, IFN-γ, and TNF-α). The results of the 16S rDNA sequencing analysis on an IlluminaMiSeq platform showed that SCP normalized Cy-induced gut dysbiosis. SCP ameliorated Cy-dependent changes in the relative abundance of several taxa, shifting the balance back to normal status (e.g., SCP increased beneficial Muribaculaceae, Ruminococcaceae, Bacteroidaceae, and Prevotellaceae while decreasing pathogenic Brevundimonas and Streptococcus). The results of this study suggest an innovative application of citrus pectin as an immunomodulator.

2018 ◽  
Vol 64 (9) ◽  
pp. 1327-1337 ◽  
Author(s):  
Songhe Guo ◽  
Linfang Li ◽  
Banglao Xu ◽  
Manghui Li ◽  
Qiuyao Zeng ◽  
...  

Abstract BACKGROUND Gut microbial dysbiosis contributes to the development of colorectal cancer (CRC). We evaluated the utility of fecal bacterial biomarker candidates identified by our 16S rDNA sequencing analysis for CRC diagnosis. METHODS We measured the relative abundance of Fusobacterium nucleatum (Fn), Faecalibacterium prausnitzii (Fp), Bifidobacterium (Bb), and Lactobacillus (Lb) by quantitative PCR in fecal samples from 2 cohorts of 903 individuals. We evaluated and validated the diagnostic performance of these microbial ratios and investigated the antagonistic effect of Fn against 3 different indicator stains. RESULTS The microbial ratio of Fn to Bb (Fn/Bb) had a superior sensitivity of 84.6% and specificity of 92.3% in detecting CRC (area under the curve, AUC = 0.911). The combination of Fn/Bb and Fn/Fp improved the diagnostic value (AUC = 0.943). Moreover, the combination of Fn/Bb and Fn/Fp offered 60.0% specificity and 90.0% sensitivity in detecting stage I of CRC (AUC = 0.804). In particular, Fn was negatively correlated with Fp in the CRC group. The performance for CRC diagnosis was confirmed in the validation cohort II. The culture supernatant from Fn exhibited strong bactericidal activity against probiotics Fp and Bb strains. CONCLUSIONS This study found that Fn could play a role in microbiota dysbiosis via the secreted antagonistic substances against probiotics. Moreover, the ratio of Fn to the important probiotics Fp and Bb was identified as a valuable biomarker for screening early CRC.


2022 ◽  
Vol 12 ◽  
Author(s):  
Sajid Ur Rahman ◽  
Haiyan Gong ◽  
Rongsheng Mi ◽  
Yan Huang ◽  
Xiangan Han ◽  
...  

Cryptosporidium parvum infection is very common in infants, immunocompromised patients, or in young ruminants, and chitosan supplementation exhibits beneficial effects against the infection caused by C. parvum. This study investigated whether chitosan supplementation modulates the gut microbiota and mediates the TLR4/STAT1 signaling pathways and related cytokines to attenuate C. parvum infection in immunosuppressed mice. Immunosuppressed C57BL/6 mice were divided into five treatment groups. The unchallenged mice received a basal diet (control), and three groups of mice challenged with 1 × 106 C. parvum received a basal diet, a diet supplemented with 50 mg/kg/day paromomycin, and 1 mg/kg/day chitosan, and unchallenged mice treated with 1 mg/kg/day chitosan. Chitosan supplementation regulated serum biochemical indices and significantly (p < 0.01) reduced C. parvum oocyst excretion in infected mice treated with chitosan compared with the infected mice that received no treatment. Chitosan-fed infected mice showed significantly (p < 0.01) decreased mRNA expression levels of interferon-gamma (IFN-γ) and tumor necrosis factor-α (TNF-α) compared to infected mice that received no treatment. Chitosan significantly inhibited TLR4 and upregulated STAT1 protein expression (p < 0.01) in C. parvum-infected mice. 16S rRNA sequencing analysis revealed that chitosan supplementation increased the relative abundance of Bacteroidetes/Bacteroides, while that of Proteobacteria, Tenericutes, Defferribacteres, and Firmicutes decreased (p < 0.05). Overall, the findings revealed that chitosan supplementation can ameliorate C. parvum infection by remodeling the composition of the gut microbiota of mice, leading to mediated STAT1/TLR4 up- and downregulation and decreased production of IFN-γ and TNF-α, and these changes resulted in better resolution and control of C. parvum infection.


Author(s):  
Jing Xia ◽  
Li Gu ◽  
Yitong Guo ◽  
Hongyan Feng ◽  
Shuhan Chen ◽  
...  

Capsaicin (CAP) is an active ingredient in chili pepper that is frequently consumed. It exerts various pharmacological activities, and also has potential effects on mental illness. However, its mechanism of antidepressant effects is still unclear. Based on the emerging perspective of the gut-brain axis, we investigated the effects of dietary CAP on gut microbes in mice with depression-like behaviors induced by lipopolysaccharide (LPS). C57BL/6J male mice (four weeks old) were given specific feed (standard laboratory chow or laboratory chow plus 0.005% CAP) for 4 months. During the last five days, LPS (0.052/0.104/0.208/0.415/0.83 mg/kg, 5-day) was injected intraperitoneally to induce depression. Behavioral indicators and serum parameters were measured, and gut microbiota were identified by sequencing analysis of the 16S gene. This study showed that dietary CAP improved depressive-like behavior (sucrose preference test, forced swimming test, tail suspension test) and levels of 5-HT and TNF-α in serum of LPS-induced mice with depression-like behaviors. In addition, CAP could recover abnormal changes in depression-related microbiota. Especially at the genus level, CAP enhanced the variations in relative abundance of certain pivotal microorganisms like Ruminococcus, Prevotella, Allobaculum, Sutterella, and Oscillospira. Correlation analysis revealed changes in microbiota composition that was closely related to depressive behavior, 5-HT and TNF-α levels. These results suggested that dietary CAP can regulate the structure and number of gut microbiota and play a major role in the prevention of depression.


Author(s):  
Hanan Alatawi ◽  
Mahmoud Mosli ◽  
Omar I. Saadah ◽  
Vito Annese ◽  
Rashad Al-Hindi ◽  
...  

The largest microbial aggregation in the human body exists in the gastrointestinal tract. The microbiota in the host gastrointestinal tract comprises a diverse ecosystem, and the intestinal microbiota plays a vital role in maintaining gut homeostasis. This study aims to examine whether the gut microbiota influences unresponsiveness to anti-TNF-α treatments in primary nonresponder patients, and consequently identify the responsible microbes as biomarkers of unresponsiveness. Stool samples were collected from a cohort of patients with an established diagnosis of IBD, either ulcerative colitis (UC) or Crohn’s disease (CD), following completion of the induction phase of anti TNF therapy. 16S rRNA sequencing analysis was used to examine the pattern of microbiota communities in fecal samples. The quality and quantity of fecal microbiota were compared in responder and primary nonresponder IBD patients following anti-TNF-α therapy. As per our hypothesis, a difference in gut microbiome composition between the two patient subgroups was observed. A decreased abundance of short-chain fatty acid (SCFA)-producing bacteria, including Anaerostipes, Coprococcus, Lachnospira, Roseburia, and Ruminococcus, was detected in non-responsive patients, which was the hallmark of dysbiosis. Biomarkers of dysbiosis that were identified as predictors of clinical nonresponse, included Klebsiella, Eubacteriaceae, RF32, Bifidobacterium_animalis, and Muribaculaceae—previously known as S24-7. Signature biomarkers showed dramatic alteration in the composition of gut microbiota in patients who demonstrated primary nonresponse to anti-TNF-α agents. Dysbiosis, with features including a dropped biodiversity, augmentation in opportunistic pathogenic microbiota, and a lack of SCFA-producing bacteria, is a prominent feature of the microbiome of primary nonresponders to anti-TNF-α therapy.


2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Zhangjian Chen ◽  
Di Zhou ◽  
Shuo Han ◽  
Shupei Zhou ◽  
Guang Jia

Abstract Background Due to its excellent physicochemical properties and wide applications in consumer goods, titanium dioxide nanoparticles (TiO2 NPs) have been increasingly exposed to the environment and the public. However, the health effects of oral exposure of TiO2 NPs are still controversial. This study aimed to illustrate the hepatotoxicity induced by TiO2 NPs and the underlying mechanisms. Rats were administered with TiO2 NPs (29 nm) orally at exposure doses of 0, 2, 10, 50 mg/kg daily for 90 days. Changes in the gut microbiota and hepatic metabolomics were analyzed to explore the role of the gut-liver axis in the hepatotoxicity induced by TiO2 NPs. Results TiO2 NPs caused slight hepatotoxicity, including clear mitochondrial swelling, after subchronic oral exposure at 50 mg/kg. Liver metabolomics analysis showed that 29 metabolites and two metabolic pathways changed significantly in exposed rats. Glutamate, glutamine, and glutathione were the key metabolites leading the generation of energy-related metabolic disorders and imbalance of oxidation/antioxidation. 16S rDNA sequencing analysis showed that the diversity of gut microbiota in rats increased in a dose-dependent manner. The abundance of Lactobacillus_reuteri increased and the abundance of Romboutsia decreased significantly in feces of TiO2 NPs-exposed rats, leading to changes of metabolic function of gut microbiota. Lipopolysaccharides (LPS) produced by gut microbiota increased significantly, which may be a key factor in the subsequent liver effects. Conclusions TiO2 NPs could induce slight hepatotoxicity at dose of 50 mg/kg after long-term oral exposure. The indirect pathway of the gut-liver axis, linking liver metabolism and gut microbiota, played an important role in the underlying mechanisms.


2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Liping Liu ◽  
Anmei Shu ◽  
Yihui Zhu ◽  
Yuping Chen

Background. Male reproductive damage, as a common complication of diabetes mellitus (DM), is getting more attention lately. We aimed to explore the protective effects and mechanism of cornuside (Cor) modulating gut microbiota to alleviate diabetes mellitus- (DM-) induced testicular damage. Methods. KK-Ay mice with reproductive damage were randomly divided into the model and Cor treatment groups, and the C57BL/6J mice were used as the normal group. These mice were orally administered Cor for 8 weeks. Results. Cor administration ameliorated the diabetes-related symptoms of polydipsia and polyphagia and lowered the fasting blood glucose (FBG) level. The results of pathological injury showed that Cor improved testicular lesions (the rupture of seminiferous tubules, degeneration of germ cells, and structural shrinkage and separation from each other) in DM model mice. Cor significantly increased the testis/body weight ratio, testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) levels in KK-Ay mice. Cor also protected from reproductive damage by inhibiting apoptosis in the testes of KK-Ay mice. Moreover, Cor significantly increased the sperm count and sperm motility. Additionally, 16S rDNA sequencing analysis showed that Cor could notably reverse the changes in the distribution of gut microbiota and decrease the abundance of Weissella confusa (Weissella), Clostridium sp. ND2 (Clostridium sensu stricto 1), uncultured bacterium (Roseburia), Anaerotruncus colihominis DSM 17241 (Anaerotruncus), [Clostridium] leptum (Anaerotruncus), unidentified (Ruminococcus 1), and uncultured bacterium (Bilophila), which may be a potential biomarker for diagnosing the testicular injury caused by DM. Meanwhile, the heat map of phylum level suggested that the testicular injury caused by DM is closely related to gut microbiota. Conclusions. Cor could alleviate DM-induced testicular damage, probably by modulating the gut microbiota.


Author(s):  
Hui Lin ◽  
Liping Meng ◽  
Zhenzhu Sun ◽  
Shiming Sun ◽  
Xingxiao Huang ◽  
...  

Background: Dietary polyphenols help to prevent cardiovascular diseases, and interactions between polyphenols and gut microbiota are known to exist. In this study, we speculated that gut microbiota-mediated metabolite regulation might contribute to the anticardiotoxic effects of yellow wine polyphenolic compound (YWPC) in doxorubicin (DOX)-treated rats. Methods: 16S-rDNA sequencing was performed to analyze the effects of YWPC on the gut microbiota in DOX-treated rats (n=6). Antibiotics were used to investigate the contribution of the altered microbiome to the role of YWPC (n=6). Plasma metabolomics were also analyzed by untargeted gas chromatography-mass spectrometry systems. Results: YWPC ameliorated DOX-mediated cardiotoxicity, as evidenced by increased cardiac and mitochondrial function and reduced levels of inflammation and myocardial apoptosis ( P <0.05 for all). The low abundance of Escherichia – Shigella , Dubosiella , and Allobaculum , along with enrichment of Muribaculaceae_unclassified , Ralstonia , and Rikenellaceae_RC9_gut_group in the gut, suggested that YWPC ameliorated DOX-induced microbial dysbiosis. YWPC also influenced the levels of metabolites altered by DOX, resulting in lower arachidonic acid and linoleic acid metabolism and higher tryptophan metabolite levels ( P <0.05 for all). Correlational studies indicated that YWPC alleviated DOX-induced inflammation and mitochondrial dysfunction by modulating the gut microbial community and its associated metabolites. Antibiotic treatment exacerbated cardiotoxicity in DOX-treated rats, and its effect on the gut microbiota partly abolished the anticardiotoxic effects of YWPC, suggesting that the microbiota is required for the cardioprotective role of YWPC. Conclusions: YWPC protected against DOX-induced cardiotoxicity in a gut microbiota–dependent manner. This supports the use of dietary polyphenols as a therapeutic approach for the treatment of cardiovascular diseases via microbiota regulation.


Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3907
Author(s):  
Sergio Pérez-Burillo ◽  
Beatriz Navajas-Porras ◽  
Alicia López-Maldonado ◽  
Daniel Hinojosa-Nogueira ◽  
Silvia Pastoriza ◽  
...  

Green tea can influence the gut microbiota by either stimulating the growth of specific species or by hindering the development of detrimental ones. At the same time, gut bacteria can metabolize green tea compounds and produce smaller bioactive molecules. Accordingly, green tea benefits could be due to beneficial bacteria or to microbial bioactive metabolites. Therefore, the gut microbiota is likely to act as middle man for, at least, some of the green tea benefits on health. Many health promoting effects of green tea seems to be related to the inter-relation between green tea and gut microbiota. Green tea has proven to be able to correct the microbial dysbiosis that appears during several conditions such as obesity or cancer. On the other hand, tea compounds influence the growth of bacterial species involved in inflammatory processes such as the release of LPS or the modulation of IL production; thus, influencing the development of different chronic diseases. There are many studies trying to link either green tea or green tea phenolic compounds to health benefits via gut microbiota. In this review, we tried to summarize the most recent research in the area.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sang-Kap Han ◽  
Yeon-Jeong Shin ◽  
Dong-Yeon Lee ◽  
Kyung Min Kim ◽  
Seo-Jin Yang ◽  
...  

Abstract Background Gut microbiota closely communicate in the immune system to maintain a balanced immune homeostasis in the gastrointestinal tract of the host. Oral administration of probiotics modulates gut microbiota composition. In the present study, we isolated Lactobacillus rhamnosus HDB1258, which induced tumor necrosis factor (TNF)-α and interleukin (IL)-10 expression in macrophages, from the feces of breastfeeding infants and examined how HDB1258 could regulate the homeostatic immune response in mice with or without lipopolysaccharide (LPS)-induced systemic inflammation. Results Oral administration of HDB1258 significantly increased splenic NK cell cytotoxicity, peritoneal macrophage phagocytosis, splenic and colonic TNF-α expression, TNF-α to IL-10 expression ratio, and fecal IgA level in control mice, while Th1 and Treg cell differentiation was not affected in the spleen. However, HDB1258 treatment significantly suppressed peritoneal macrophage phagocytosis and blood prostaglandin E2 level in mice with LPS-induced systemic inflammation. Its treatment increased LPS-suppressed ratios of Treg to Th1 cell population, Foxp3 to T-bet expression, and IL-10 to TNF-α expression. Oral administration of HDB1258 significantly decreased LPS-induced colon shortening, myeloperoxidase activity and NF-κB+/CD11c+ cell population in the colon, while the ratio of IL-10 to TNF-α expression increased. Moreover, HDB1258 treatment shifted gut microbiota composition in mice with and without LPS-induced systemic inflammation: it increased the Cyanobacteria and PAC000664_g (belonging to Bacteroidetes) populations and reduced Deferribacteres and EU622763_s group (belonging to Bacteroidetes) populations. In particular, PAC001066_g and PAC001072_s populations were negatively correlated with the ratio of IL-10 to TNF-α expression in the colon, while the PAC001070_s group population was positively correlated. Conclusions Oral administered HDB1258 may enhance the immune response by activating innate immunity including to macrophage phagocytosis and NK cell cytotoxicity in the healthy host and suppress systemic inflammation in the host with inflammation by the modulation of gut microbiota and IL-10 to TNF-α expression ratio in immune cells.


Author(s):  
Shien Ren ◽  
Chao Fan ◽  
Liangzhi Zhang ◽  
Xianjiang Tang ◽  
Haibo Fu ◽  
...  

Abstract Plants produce various plant secondary compounds (PSCs) to deter the foraging of herbivorous mammals. However, little is known about whether PSCs can reshape gut microbiota and promote gut homeostasis of hosts. Using 16S rDNA sequencing to investigate the effects of PSCs on the gut microbiota of small herbivorous mammals, we studied plateau pikas (Ochotona curzoniae) fed diets containing swainsonine (SW) extracted from Oxytropis ochrocephala. Our results showed that both long- and short-term treatment of a single artificial diet in the laboratory significantly reduced alpha diversity and significantly affected beta diversity, core bacteria abundance, and bacterial functions in pikas. After SW was added to the artificial diet, the alpha diversity significantly increased in the long-term treatment, and core bacteria (e.g., Akkermansiaceae) with altered relative abundances in the two treatments showed no significant difference compared with pikas in the wild. The complexity of the co-occurrence network structure was reduced in the artificial diet, but it increased after SW was added in both treatments. Further, the abundances of bacteria related to altered alanine, aspartate, and glutamate metabolism in the artificial diet were restored in response to SW. SW further decreased the concentration of short-chain fatty acids (SCFAs) in both treatments. Our results suggest that PSCs play a key role in regulating gut microbiota community and intestinal homeostasis, thereby maintaining host health. Key points • Swainsonine improves the intestinal bacterial diversity of plateau pikas. • Swainsonine promotes the recovery of core bacterial abundances in the gut of plateau pikas. • Swainsonine promotes the restoration of intestinal bacterial functions of plateau pikas.


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